PHOSPHOLIPASE B: A VIRULENCE FACTOR FOR CANDIDA GLABRATA

描述（改编自申请摘要）：在本K08申请中， 科尼利厄斯克兰西要求3年的支持，以学习必要的技能， 实现他成为一名成功的临床科学家的职业目标。 的 申请人的长期研究兴趣是识别和研究 酵母病原体光滑念珠菌的毒力因子，现在是一个主要的 血液真菌感染在美国。 C. glabrata是一个模型 研究分子遗传学的生物，因为它有一个单倍体基因组， 与酿酒酵母关系密切。 申请人的实验室 细胞外磷脂酶B（PL B）活性水平与 C的严重性。人类的光滑侵入性感染。 他假设， 基因cgPLB2负责大部分C. glabrata的PLB活性，以及 cgPLB2的破坏将显著降低病毒的毒力， 有机体 申请人的短期目标是最终证明， cgPLB2通过实现Koch's的分子形式而在毒力中是重要的。 假设 具体来说，他将完成cgPLB2的克隆，证明 由cgPLB2破坏引起的PLB活性降低减弱了毒力 在弥散性感染小鼠模型中，并证明了恢复 通过重新插入cgPLB2的PLB活性恢复毒力。 在完成 在这个项目中，他将学习广泛的分子生物学技术， 生物化学和播散性感染的动物模型。 此外他 将学习制定假设，设计适当的实验，应用 统计工具，并解释数据。 这些技能将得到补充， 包括基础科学课程和高级研讨会的教育计划 和统计数据。 他将在一个多学科的 医学系和系资源支持的环境 佛罗里达大学的分子遗传学和微生物学， 他的导师阿尔弗雷德·列文（Alfred Lewin）（一位酵母遗传学家）和他的共同导师密切合作， 弗雷德里克·索斯威克（Frederick Southwick）是传染病科主任，微生物研究专家， 发病机理和细胞生物学）。

DESCRIPTION (adapted from application abstract): In this K08 application, Cornelius Clancy requests 3 years of support to learn the skills necessary to achieve his career goal of becoming a successful clinician-scientist. The applicant's long-term research interest is in identifying and studying virulence factors for the yeast pathogen Candida glabrata, now a leading bloodstream fungal infection in the United States. C. glabrata is a model organism for studying molecular genetics because it has a haploid genome and is closely related to Saccharomyces cerevisiae. The applicant s laboratory has correlated levels of extracellular phospholipase B (PLB) activity with the severity of C. glabrata invasive infections in humans. He hypothesizes that the gene cgPLB2 is responsible for much of C. glabrata s PLB activity, and that disruption of cgPLB2 will significantly reduce the virulence of the organism. The applicant s short-term goal is to conclusively prove that cgPLB2 is important in virulence by fulfilling the molecular form of Koch's postulates. Specifically, he will finish cloning cgPLB2, demonstrate that the reduction of PLB activity caused by disruption of cgPLB2 attenuates virulence in a murine model of disseminated infection, and demonstrate that restoration of PLB activity by reinsertion of cgPLB2 restores virulence. In completing this project, he will learn a wide range of techniques in molecular biology, biochemistry, and animal models of disseminated infections. In addition he will learn to formulate hypotheses, design appropriate experiments, apply statistical tools, and interpret data. These skills will be complemented by an educational plan including courses and advanced seminars in basic sciences and statistics. He will receive this training in a multidisciplinary environment supported by the resources of the Dept of Medicine and the Dept of Molecular Genetics and Microbiology at the University of Florida, guided closely by his mentor, Alfred Lewin (a yeast geneticist) and his co-mentor, Frederick Southwick (Chief of Infectious Diseases and an expert in microbial pathogenesis and cell biology).